The purpose of these studies is to define the neurohormonal control of esophageal motility in order to provide an understanding of the pathogenesis of esophageal motor disorders. Opossum is used as an experimental model because of the similarity of opossum esophagus to that of man. We have shown that lower esophageal sphincter closure at rest is due to tonic intrinsic myogenic activity of the sphincter muscle. The main role of the vagus nerve is to cause sphincter inhibition. We are now examining the nature of the inhibitory transmitter. We have shown that the inhibitory transmitter is neither acetylcholine, nor a catecholamine. Dopamine, histamine and seratonin are excluded as possibilities. Now we plan to examine ATP and related purines, prostaglandins, peptides (VIP, neurotensin) and aminoacids as possible inhibitory transmitters of vagally mediated inhibition of the lower esophageal sphincter.